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Biomedical subjects

N Salem

Publications and source records attributed to N Salem.

At least 55 records · Page 3Linked to original sources
PubMed2000

Long chain polyunsaturated fatty acid formation in neonates: effect of gestational age and intrauterine growth.

The present study was designed to evaluate the effect of gestational age and intrauterine growth on the long chain polyunsaturated fatty acid (LCP) synthesis from dietary precursors in neonates as reflected by plasma pools. These have been considered conditionally essential nutrients for normal growth, sensory maturation, and neurodevelopment. In vivo elongation/desaturation of deuterated d5-linoleic acid (d5-LA) to form arachidonic acid (AA), and d5-alpha-linolenic acid (d5-LNA) to form docosahexaenoic acid (DHA), was studied in 19 preterm appropriate-for-gestational-age (AGA) infants, 11 AGA term, and 11 intrauterine growth-retarded (IUGR) infants. They received a dose of 50 mg/kg body weight of d5-LA and d5-LNA enterally during the first days of life; d5-labeled derivatized fatty acids were determined in blood samples obtained at 24, 48, and 96 h after dosing. Lipids were extracted and fatty acids analyzed by gas chromatography and negative ion mass spectrometry. Mean concentrations, microg/mL, and d5/d0 for n-3 and n-6 precursor and products were computed at various times and were also integrated over the complete study period. Significantly higher time-integrated concentration of d5-AA and d5-DHA were observed in preterm infants relative to the other two groups. Time-integrated enrichment of DHA relative to LNA was 100-fold lower in preterms, 410-fold lower in term, and 27-fold lower in IUGR infants. Similar significant declines in product to precursor enrichments were noted for the n-6 series. A significant negative correlation of AA and DHA formation based on time-integrated d5/d0 ratios with gestational age was noted; product/ precursor enrichment versus gas chromatography for the n-6 series had an r of -0.5, p = 0.001, and for the n-3 series had an r of -0.6, p = 0.0001. Birth weight or weight adequacy did not add further strength to the relationship. We conclude that LCP formation from deuterated precursors occurs as early as 26 wk gestation, and in fact is more active at earlier gestational ages; growth retardation appears to slow down or diminish LCP formation. No quantitative estimates of LCP synthesis or nutritional sufficiency can be derived from these data.

Embryonic and Fetal Development↗
PubMed2000

[Autosomal dominant Mendelian midline complex. Secundum atrial septal defect associated with cardiac and facial-thoracic defects. A familial case].

The kindred of 38 individuals reported here have various anomalies: 1. facio-thoracic malformations: hypertelorism, nasal deviation, cleft lip and palate, upper-incisors diastema and pectus excavatum; 2. cardiac anomalies: sinus node bradycardia, atrial fibrillation, nodal rhythm, atrial septal defect. Wolff-Parkinson-White syndrome, low insertion of the septal tricuspid valve corresponding to an Ebstein syndrome, pulmonic "en dôme" valve stenosis, aortic valve stenosis, long QT, and intraventricular conduction blocks. Almost all these defects are septal or para-septal. Mitral stenosis is probably rheumatoid. Such median varied pathology has not been yet reported. All the extra-cardiac anomalies are situated along the vertical upper half-body midline. All cardiac anomalies are in the septal or para-septal region. It is an autosomal dominant trait that implies the early embryonic development of the midline of cardiac and extra-cardiac structures.

Abnormalities, Multiple↗
PubMed2000

Prostate cancer radiosensitization in vivo with adenovirus-mediated p53 gene therapy.

An adenovirus 5 vector containing wild-type p53 cDNA (Ad5-p53) and a cytomegalovirus promoter was used to generate p53 transgene expression. Control vector (Ad5-pA) contained the poly-adenosine sequence. PC3 cells (2 x 10(6)) were injected s.c. into the legs of nude mice. Treatment with Ad5-p53 was initiated at a tumor volume of 200 mm3. Three intratumoral injections (days 1, 4, and 7) were given with 3 x 10(8) plaque-forming units, followed by 5 Gy pelvic irradiation (day 8) in one fraction using a cobalt-60 source. Tumor volume measurements were obtained every 2 days. LNCaP cells (2 x 10(6)) were injected orthotopically into the prostates of nude mice, and tumor weight was approximated using serum prostate-specific antigen (PSA) obtained from weekly tail vein bleedings. The target PSA for the start of the studies was 5 ng/ml. The intraprostatic injections of Ad5-p53 were done twice (days 1 and 2) and followed by 5 Gy pelvic irradiation on day 3. The PC3 tumor volume growth curves were log transformed and fitted using linear regression. The times (in days) for the tumors to reach 500 mm3 were calculated as 10.7 +/- 0.7 (+/- SE) for the saline control (no virus), 9.8 +/- 2.1 for Ad5-pA, 15.6 +/- 1.6 for Ad5-p53, 14.6 +/- 1.5 radiation therapy (RT; 5 Gy), 14.6 +/- 1.5 for Ad5-pA plus RT, and 31.4 +/- 5.3 for Ad5-p53 plus RT. The Ad5-p53 plus RT times were significantly different from the other groups. An enhancement factor of 3.4 was calculated, indicating supra-additivity. LNCaP tumor growth was determined via weekly serum PSA measurements. Treatment failure was determined using two PSA-based methods; a serum PSA of > 1.5 ng/ml or two rises in PSA during 6 weeks posttreatment. The results were similar using either end point. Treatment with Ad5-p53 plus 5 Gy resulted in significantly fewer PSA failures (<30%), as compared with Ad5-p53 alone (64-73%) and the other controls (approximately 80-100%) These results are also consistent with a supra-additive inhibition of tumor growth. Tumor growth in vivo was inhibited supra-additively when p53null and p53wildtype prostate tumors were treated with Ad5-p53 and 5 Gy radiation.

Adenoviridae↗
PubMed1999

Autosomal dominant secundum atrial septal defect with various cardiac and noncardiac defects: a new midline disorder.

We report on a Lebanese family in which 12 persons had an atrial septal defect and various cardiac and noncardiac anomalies. Cardiac anomalies are left axis deviation of QRS, right bundle branch block, atrial fibrillation, Wolff-Parkinson-White syndrome, nodal atrioventricular rhythm, aortic stenosis, pulmonic valve stenosis, mitral stenosis (Lutembacher syndrome), and low implantation of the tricuspid valve (Ebstein disease). Noncardiac abnormalities consisted specially of the presence of hypertelorism, cleft lip, and pectus excavatum. This combination appears to constitute a hitherto undescribed autosomal dominant midline disorder of the heart and upper half of the body with almost full penetrance and variable expressivity. The mutation does not map to any known locus involved in atrial septal defect or conduction block.

Abnormalities, Multiple↗
PubMed1999

A chronic ethanol-feeding study in rhesus monkeys.

This study describes the effect of chronic ethanol-feeding in rhesus monkeys. Animals which were maintained on a diet containing 18:2n-6 and 18:3n-3 as 1.4 and 0.08% of the calories, respectively, and consumed alcohol (mean 2.6 g kg(-1) d(-1)) had decreased amounts of 20:4n-6 and 22:6n-3 in their livers and plasma lipids compared with controls. Alcohol consumption did not appear to effect the absorption of 2H(5)-18:2n-6 and 18:3n-3 esters into the blood following an oral dose. There was an increase in 2H5 enrichment in plasma 20:4n-6 and 22:6n-3, indicating that alcohol may have increased production of these fatty acids. There was a greater concentration of 4-hydroxynonenal in the plasma of alcohol-exposed monkeys compared to controls.

Alcoholism↗
PubMed1999

Rats with low levels of brain docosahexaenoic acid show impaired performance in olfactory-based and spatial learning tasks.

Studies were carried out to determine if decreased levels of central nervous system docosahexaenoic acid (DHA), a result of consuming an n-3-deficient diet, had an effect on learning- and memory-related behaviors in adult male rats. Females were reared on an n-3-deficient or n-3-adequate diet beginning at 21 d of life. Their male pups, the F2 generation, were weaned to the diet of the dam and tested at 9-12 wk of age. An olfactory-based discrimination and Morris water maze task were used to assess performance. Whole brain was collected after the behavioral experiments and central nervous system fatty acid content was analyzed in olfactory bulb total lipid extracts. F2 generation male rats consuming the n-3-deficient diet had an 82% decrease in DHA compared to rats consuming the n-3-adequate diet. The n-3-deficient animals made significantly more total errors in a 7-problem, 2-odor discrimination task compared to the n-3-adequate group. Furthermore, the escape latency in the Morris water maze task was significantly longer for the n-3-deficient rats compared to the n-3-adequate rats. These results indicate that rats with decreased DHA levels in the central nervous system perform poorer in these tasks compared to rats with higher DHA levels and suggest the presence of learning deficits in these animals.

Animals↗
PubMed1999

A mutation in OTOF, encoding otoferlin, a FER-1-like protein, causes DFNB9, a nonsyndromic form of deafness.

Using a candidate gene approach, we identified a novel human gene, OTOF, underlying an autosomal recessive, nonsyndromic prelingual deafness, DFNB9. The same nonsense mutation was detected in four unrelated affected families of Lebanese origin. OTOF is the second member of a mammalian gene family related to Caenorhabditis elegans fer-1. It encodes a predicted cytosolic protein (of 1,230 aa) with three C2 domains and a single carboxy-terminal transmembrane domain. The sequence homologies and predicted structure of otoferlin, the protein encoded by OTOF, suggest its involvement in vesicle membrane fusion. In the inner ear, the expression of the orthologous mouse gene, mainly in the sensory hair cells, indicates that such a role could apply to synaptic vesicles.

Amino Acid Sequence↗
PubMed1999

Alcohol consumption in rhesus monkeys depletes tissues of polyunsaturated fatty acids and alters essential fatty acid metabolism.

Rhesus monkeys that were maintained on an adequate diet but with low levels of essential fatty acids (1.4 en% linoleic, 18:2n-6, and 0.08 en%, linolenic acid, 18:3n-3) became depleted of 20:4n-6, and 22: 6n-3 in their livers, plasma lipoproteins, and erythrocytes during an 18-month period of alcohol exposure (2.6 g kg(-1) day(-1)). Monkeys that consumed alcohol also had higher plasma concentrations of 4-hydroxynonenal compared to controls. The metabolism of 18:2n-6 and 18:3n-3 were evaluated in both groups of animals using deuterium-labeled substrates over a 9-day period. Alcohol consumption did not appear to have an effect on the absorption of either 2H5-18:2n-6 or 2H5-18:3n-3 ethyl esters into the circulation after a single oral dose. However, there was a greater enrichment of deuterium in the biosynthesized fatty acids, 20:4n-6 and 22:6n-3, in the plasma of the monkeys exposed to alcohol compared to controls. These results suggest that chronic alcohol exposure may lead to a stimulation of the rate at which long-chain polyunsaturated fatty acids are biosynthesized to compensate for an increase in lipid peroxidation.

Aldehydes↗
PubMed1998

Essential fatty acids predict metabolites of serotonin and dopamine in cerebrospinal fluid among healthy control subjects, and early- and late-onset alcoholics.

BACKGROUND: Impulsive violence, suicide, and depression are strongly associated with low concentrations of cerebrospinal fluid 5-hydroxyindoleacetic acid (CSF 5-HIAA). Increased suicide and trauma reported in some cholesterol-lowering trials may be related to altered concentrations of polyunsaturated fatty acids rather than cholesterol, a possible surrogate marker. METHODS: CSF 5-HIAA and homovanillic acid (HVA), total cholesterol, and plasma fatty acid concentrations were examined in 176 subjects, including 49 healthy volunteers, and 88 early- and 39 late-onset alcoholics. RESULTS: Among each group, polyunsaturated fatty acids predicted both CSF 5-HIAA and CSF HVA concentrations, but total cholesterol was unrelated to either neurotransmitter metabolite. The relationships between plasma 22: 6n3 and CSF 5-HIAA were significantly different when healthy volunteers (r = .35) were compared to early-onset alcoholics (r = -.38) (p < .0002). CONCLUSIONS: Dietary studies are indicated to determine if essential fatty acid supplementation can influence central nervous system serotonin and dopamine metabolism and modify impulsive behaviors related to these neurotransmitters.

Adult↗
PubMed1998

A replication study of violent and nonviolent subjects: cerebrospinal fluid metabolites of serotonin and dopamine are predicted by plasma essential fatty acids.

BACKGROUND: Among an independent group of subjects selected for their history of violent, impulsive behaviors and nonviolent control subjects, we attempted to replicate the finding that plasma docosahexaenoic acid concentrations were negatively correlated with cerebrospinal fluid 5-hydroxyindoleacetic acid (CSF 5-HIAA) concentrations. METHODS: CSF 5-HIAA and homovanillic acid (HVA), fasting total cholesterol, and plasma fatty acid concentrations were examined in violent and nonviolent subjects matched for their severity of alcohol dependence. RESULTS: Violent subjects had significantly higher lifetime violence and hostility ratings and lower concentrations of CSF 5-HIAA than nonviolent subjects. Plasma docosahexaenoic acid was negatively correlated with CSF 5-HIAA only among violent subjects. CONCLUSIONS: This observational study suggests that dietary essential fatty acids may change neurotransmitter concentrations. Prospective dietary intervention trials will be required to determine if increasing dietary intake of docosahexaenoic acid will increase or decrease either CSF 5-HIAA concentrations or impulsive and violent behaviors.

Adult↗
PubMed1998

[Comparison of the effect of subcutaneous injection of adrenaline and terbutaline in asthma crisis in infants].

BACKGROUND: Edema of the mucous membranes lining the airways is a major factor of airway obstruction in asthma. Stimulation of both alpha and beta-adrenergic receptors is thus logically useful to reduce edema through vasoconstriction and to cause smooth muscle relaxation. The aim of this work was to compare the effects of subcutaneous epinephrine vs terbutaline for treating acute attack of asthma in infants. PATIENTS AND METHODS: Fifty-four infants aged less than 30 months admitted for acute asthma attacks were included in this study. None had previous cardiovascular or definite pulmonary disease and none had tachycardia above 200/min. The patients were randomly given subcutaneous epinephrine, 10 micrograms/kg (n = 28) or subcutaneous terbutaline at the same dosage (n = 26). RESULTS: Improvement in accessory muscle use, oxygen saturation, PaO2 and PCO2 was similar in both groups. The respiratory rate was significantly improved after administration of epinephrine (P = 0.05). No adverse effects were seen in either drug. CONCLUSION: Subcutaneous administration of epinephrine is as effective as terbutaline in treating acute attack of asthma in infants. This drug, easy to use and of low-cost, could be the treatment of choice in developing countries.

Asthma↗
PubMed1998

[Chemotherapy of soft tissue sarcoma in the adult].

The goal of postoperative treatment in adult soft tissue sarcoma is local control, and in high-risk patients prevention of distant failures. Radiation therapy is essential after non-radical surgery. The role of adjuvant chemotherapy on improvement of overall survival remains to be evidenced; however, recent meta-analysis data have confirmed its impact on both local and metastatic evolution of the disease. Because for both radiotherapy and chemotherapy, delay of treatment may be crucial for efficacy following tumor excision, concomitant radiochemotherapy should be considered. Review of the literature as well as personal results showed the feasibility of postoperative radiochemotherapy in adult soft tissue sarcoma, even when the chemotherapeutic associations used included an anthracycline. Prospective study of radiochemotherapy should be performed in order to assess its real impact in terms of efficacy and toxicity.

Adult↗
PubMed1998

A v-SNARE participates in synaptic vesicle formation mediated by the AP3 adaptor complex.

Reconstitution of synaptic vesicle formation in vitro has revealed a pathway of synaptic vesicle biogenesis from endosomes that requires the heterotetrameric adaptor complex AP3. Because synaptic vesicles have a distinct protein composition, the AP3 complex should selectively recognize some or all of the synaptic vesicle proteins. Here we show that one element of this recognition process is the v-SNARE, VAMP-2, because tetanus toxin, which cleaves VAMP-2, inhibited the formation of synaptic vesicles and their coating with AP3 in vitro. Mutant tetanus toxin and botulinum toxins, which cleave t-SNAREs, did not inhibit synaptic vesicle production. AP3-containing complexes isolated from coated vesicles could be immunoprecipitated by a VAMP-2 antibody. These data imply that AP3 recognizes a component of the fusion machinery, which may prevent the production of inert synaptic vesicles.

Adaptor Protein Complex 3↗